ABSTRACT

Background

Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients’ susceptibility to developing liver cirrhosis or their responsiveness to the treatment.

Aim

We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs).

Methods

IFN-γ (+874T/A, +2109A/G) and IP-10 (−135G/A, −1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods.

Results

IFN-γ + 874 TA, IP-10 − 135AA, and IP-10 − 1447AA and IP-10 − 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci −135 and −1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D’ = 0.999, r² = 0.689).

Conclusion

Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.

中文翻译：

---

干扰素-γ (IFN-γ) 和 IFN-γ-诱导蛋白 10 (IP-10) 基因多态性对丙型肝炎病毒相关肝硬化风险的影响

摘要

背景

如今，越来越多的证据表明促炎细胞因子中的个体遗传多态性与慢性丙型肝炎 (CHC) 严重程度之间存在关联。已经证明，某些基因的多态性可以显着预测 HCV 感染患者对发展为肝硬化的易感性或其对治疗的反应。

目标

我们研究了干扰素 (IFN-γ) 和干扰素γ诱导蛋白 10 (IP-10) 基因中的单核苷酸多态性 (SNP) 对 HCV 感染患者肝硬化风险的影响及其与对各种直接作用抗病毒药物的反应的关系药物（DAA）。

方法

IFN-γ (+874T/A, +2109A/G) 和 IP-10 (-135G/A, -1447A/G) 基因型在 175 名 CHC 埃及 HCV 患者（69 名肝硬化和 106 名非肝硬化患者）中使用单链多态性聚合酶链反应 (SSP-PCR) 或限制性片段长度-PCR (RFLP-PCR) 方法。

结果

与非肝硬化患者相比，发生肝硬化的患者的 IFN-γ + 874 TA、IP-10 - 135AA 和 IP-10 - 1447AA 和 IP-10 - 1447GG 基因型增加。虽然，它们的分布没有显示出统计学意义，表明这些 SNP 与 HCV 感染患者的肝硬化易感性之间缺乏关联。对所有选定基因的不同基因座之间的单倍型分析显示，肝硬化患者的 AGGA 和 TAGA 显着增加，而 TGGA 单倍型显着减少。IP-10 的基因座 -135 和 -1447 的基因型频率似乎处于完全连锁不平衡 (LD) (D' = 0.999, r ²  = 0.689)。

结论

我们的数据支持这样的概念，即 IFN-γ 和 IP-10 基因多态性不是埃及 HCV 感染患者疾病进展的预测因子。